ENCePP Guide on Methodological Standards in Pharmacoepidemiology

10.1.3. Prominent issues in CER

10.1.3.1. Randomised clincial
trials vs. observational studies

While RCTs are considered to
provide the most robust evidence of the efficacy of therapeutic options, they
are affected by well-recognised qualitative and quantitative limitations that
may not reflect how the drug of interest will perform in real-life. Moreover,
relatively few RCTs are traditionally designed using an alternative therapeutic
strategy as a comparator, which limits the utility of the resulting data in
establishing recommendations for treatment choices. For these reasons, other
research methodologies such as pragmatic trials and observational studies may
complement traditional explanatory RCTs in CER.

A model based on counterfactual
theory for CER using large administrative healthcare databases has been
suggested, in which causal inference from observational studies based on large
administrative health databases is viewed as an emulation of a randomized trial.
This ‘target trial’ is made explicit and design and analytic approaches are
reviewed in Using
Big Data to Emulate a Target Trial When a Randomized Trial Is Not
Available (Am J Epidemiol (2016) 183 (8): 758-764).

10.1.3.3. Bias and confounding
in observational CER

Methodological issues and
principles of Section 5 of the ENCePP Guide are applicable to CER as well and
the textbooks cited in that chapter are recommended for consultation.